Chronic renal failure patients who are presensitized to histocompatibility antigens, presumably through exposure by pregnancy, blood transfusion and perhaps bacterial infections, have a documented high failure rate of kidney transplants. Presensitization seems to have more influence on the outcome of transplantation than does matching of donors and recipients by HL-A antigens. The routine method for detection of presensitization is relatively insensitive and recognizes only complement dependent antibody to HL-A. There are data to suggest that other functional antibody classes are raised in response to histocompatibility antigens and that these are manifestations of presensitization that also could prejudice survival of a transplant. There are data to indicate that presensitization can be reflected in certain cell-mediated immune responses and this form of presensitization is not routinely assessed. The program is directed to improved detection of presensitization by a coordinated study of complement-dependent lymphocytotoxins, lymphocyte-dependent antibody, mixed-leukocyte culture blocking antibody, heterophile antibody and direct cell-mediated lymphocytotoxicity in chronic renal failure patients and transplant recipients. The specificities of these antibody classes will be studied using a program of cross absorptions. The incidence and specificity of antigen presensitization as well as immune-responder status, will be correlated with the outcome of kidney transplants and with other parameters such as immunologic adaptation.